The objective of the Craniofacial Anomalies Research Center is to identify human genes and other risk factors important in the etiology of craniofacial anomalies, particularly orofacial clefting. This objective will be achieved through four interrelated projects and two cores. Project 1 will expand the Iowa case control study of facial clefts to additional states to obtain a more diverse study population that will be large enough to evaluate the interaction of genetic and environmental causes of cleft lip and palate. Project 2 will identify human genes involved in craniofacial anomalies, including several Mendelian disorders, utilizing modern genetic analytical techniques. Project 3 will identify and characterize novel genes involved in craniofacial development, utilizing a subtracted human fetal craniofacial cDNA library and the differential RNA display approach. Project 4 will study the function of several candidate genes identified in projects 2 and 3 by gene targeting and transgenic mouse technologies. These projects will be supported by a core offering administrative support and a core providing services in molecular biology and the establishment of cell lines from various patients.